The Center for Mass Spectrometry and Proteomics (CMSP) at the University of Minnesota (UMN) requests a next-generation Orbitrap Tribrid mass spectrometer and HPLC system, equipped with High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) and electron transfer dissociation (ETD) technologies. This instrument will provide transformative technologies for advancing dozens of NIH and other externally-funded, ongoing projects, as well as catalyzing new research directions for investigators at the UMN and the Upper Midwest region. The instrument will be placed in the well-established and supported CMSP core facility at the UMN, which serves hundreds of researchers at the UMN as well as investigators from numerous institutions across the region. The new Orbitrap Tribrid will address current limitations in both performance and throughput in the CMSP -- replacing an Orbitrap Velos instrument, installed in 2011 and currently the only full-time instrument dedicated to proteomics studies in the CMSP. The combined capabilities of the newly redesigned Tribrid instrument, equipped with FAIMS and ETD, will be a game-changing platform, accelerating discoveries for a broad-array of biomedical studies. Guided by the requirements of the numerous NIH-supported projects, the new instrument platform will extend capabilities in these areas: 1) Quantitative proteomics, including the emerging area of data-independent acquisition (DIA); 2) Post-translational modifications (PTMs); and 3) Next generation multi-omic applications, integrating genomic-proteomic data (proteogenomics and metaproteomics); 4) Lipid and small molecule isomer analysis, a value-added application in addition to proteomics enabled by the capabilities of FAIMS coupled with the Orbitrap analyzer. We detail 9 major projects which will be significantly advanced by the requested instrument, as well as 9 minor projects. The majority of these projects are ongoing NIH-supported studies. In addition, the requested instrument will be the only Orbitrap Tribrid equipped with FAIMS and ETD housed within an accessible core facility in the Upper Midwest region, further broadening the impact of this system. Once in place, this cutting-edge technology will accelerate new and important discoveries for dozens of ongoing NIH-supported research studies, as well as open new directions of research and inquiry in biomedical studies at the UMN and across the Upper Midwest, impacting diverse studies of human health and disease.